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The population pharmacokinetic analysis is a relatively new approach, which can be used to obtain the pharmacokinetic and/or pharmacodynamic information required to make rational decision about the magnitude of an initial dose for a given patient, and of a subsequent dose if adjustment is needed. The present article reviews our recent effort for population pharmacokinetics, focusing on the analyzes of digoxin disposition in the elderly and of phenytoin disposition in children. The population pharmacokinetic parameters of digoxin were estimated using 689 routine therapeutic drug monitoring data from 243 patients. A three-step approach combining Bayesian regression and nonlinear mixed effect analysis was useful for estimating population parameters of digoxin. On the other hand, a simulation study showed that the one-compartment model with dose-dependent clearance should be considered for estimating Michaelis-Menten elimination kinetics. Then, the population pharmacokinetic parameters of phenytoin were estimated using 531 routine therapeutic drug monitoring data from 116 epileptic patients. In addition, we showed that the genetic polymorphism of CYP2C isoenzymes plays an important role in the pharmacokinetic variability of phenytoin. The population pharmacokinetic approach was useful for analyzing the pharmacogenetics of phenytoin.

Population Analysis of the Pharmacokinetic Variability in Children and the Elderly.